Current Treatment Landscape of Ovarian Cancer with Dr. Sharyn Lewin

Surgical Staging and Upfront Biomarker Testing Hello everyone, and welcome back to the Oncology Brothers Podcast. I'm Rohed Ghosain here with my younger brother and Co host Rahul Ghosain. Today we're walking through the evolving treatment landscape of ovarian cancer. We've seen few advances in this disease, which we will touch on, but also we will dive into the world of germline testing, role of chemotherapy, PARP inhibitors and even immunotherapy to walk us through the treatment algorithm for ovarian cancer. In 2025, we are excited to have Doctor Sharon Lewin, the director of gynecology oncology at the Holy Name Medical Center. Sharon, thanks so much for joining us. Speaker 2 Thank you for having me. Speaker 3 Sharon, welcome. Before we jump right in, I have to acknowledge that often as a medical oncologist, we have limited exposure to Gynonk in our fellowship training. But then out in the community, we often do see these patients in our clinic. So discussion around ovarian, endometrial or cervical cancer always are enlightening for me. OK, so with that disclaimer, let's get started. When it comes to ovarian cancer, this disease is surgically staged and debunking surgery, if possible is where we often start. This is how we also get our Phygo staging. If upfront surgery is not possible, then we can rely on periop or neoadjuvant systemic treatment. Sharon, can you start us here? For suspected ovarian cancer, a patient who has undergone surgery, what is your work up? Does this include a front NGS? We know that germline testing is now recommended for any patient with ovarian cancer. And then once you have all this information, what is your systemic treatment paradigm? A front. Speaker 2 These are really excellent questions. So when you look at all of the literature, the gold standard if we can, is to still offer surgery first upfront debulking is really to remove all gross residual disease and then have adjuvant treatment. For surgery to really benefit women, they need to have a complete cyto reduction. We've seen that more and more oncologists and patients are shifting towards the neoadjuvant approach for various reasons, and also looking at disease biology and how the literature is interpreted. And more and more we've seen in the literature and especially some of the ASCO guidelines that women in the United States are actually getting neoadjuvant chemotherapy. Platinum based chemotherapy is still the standard of care for women, Carboplatinum and Taxol. It's very important that if women do have neoadjuvant chemotherapy, we get enough tumor up front so that we can do this biomarker testing and molecular profiling. As you mentioned, germline testing is really the standard of care for all women with epithelial ovarian cancer. Even though NCCN has said for over a decade now that all women with epithelial ovarian cancer have germline testing, We see from recent GCO publications that only about 60% of women with ovarian cancer are actually getting upfront germline testing. So that's really critically important for our maintenance decisions when it comes to PARP inhibitors, which we'll talk about in a moment. So if you're going to start neoadjuvant chemotherapy and you're using IR for a biopsy, for example, we've been advocating to get at least 6 to 8 core passes with an 18 gauge needle so that not only can you get enough tissue or tumor for the core biopsy to confirm the diagnosis, but to do HRD testing with a reputable company and the next Gen. sequencing, you know, before you start chemotherapy. Some of these women who have HRD, which is about half of women with epithelial ovarian cancer, will have such a robust response to initial platinum based chemotherapy that if you wait to test them till their interval cycle reduction, you may have lost the opportunity to do HRD testing. If patients do have an upfront surgery, then they definitely have at least six cycles of platinum based chemotherapy. We can talk about the role of bevacizumab because that's important to discuss. It is standard for these women who have a germline BRCA mutation or a somatic BRCA or HRD in their tumors to then have part maintenance following adjuvant treatment. Speaker 3 You know, when we're talking about neoadjuvant or adjuvant, we're often chasing the idea of 69 cycles. In my practice, if I've given 3 or 4 cycles of fun, then I'm making up for that in adjuvant settings. Maintenance Strategies with PARPs and Bevacizumab This is a good segue to talk through maintenance options. Sharon, you've touched on bevacizumab. We also have your apartment inhibitors. You have 3 available. How are you deciding on who gets bevacizumab versus combining that with your apartment inhibitors and which park inhibitor? What data do you have for that? Speaker 2 This is a really excellent question and one that is discussed and debated quite a bit among GYN oncologist. I've sort of changed my own practice over the years. I rely a lot on the Paulo One data which was initially released in 2019. That was a European registration trial which looked at upfront bevacizumab in patients with stage 3 and 4 ovarian cancer. There was a post hoc analysis in that subset of patients looking at the higher and lower risk subset of these stage 3 and four women with advanced ovarian cancer. Based on that post hoc analysis, I changed my practice pattern. How I have looked at all the literature myself based on Paula, Paula One, I tend to start all of my patients on bevacizumab with platinum BEAST chemotherapy, whether it's neoadjuvant or adjuvant. And you have to think about the timing around surgery. If a patient does have HRD, then in the maintenance phase, I continue the bevacizumab and add a lap rib. At that point if she does not have HRDI will just continue the bevacizumab alone as maintenance. But again, in Palo One, looking at this higher and lower risk subgroup, we saw an impressive PFS and even OS benefit in the higher and lower risk patients. For newly diagnosed patients, I use the PARP inhibitors, specifically a lab rib for patients who have a germline BRC mutation based on Solo one or somatic BRC mutation also based on solo one for two years as maintenance following frontline treatment or the patients who have HRD in their tumors, which is about half of all women with ovarian cancer. That's based on Palo One. That's subpopulation of patients had bevacizumab with platinum based chemotherapy and then in the maintenance phase continued bevacizumab for 15 months and had the elaborab added on for two years. So it's really the germline somatic positive or mutated patients and then the HRD positive patients, we're only allowed to use Parps if a patient has a BRCA mutation or has HRD. The label has changed. So I think that's an important point to mention since this podcast has gone out just so you know that that FDA required GSK to change their label, which highlights the importance of biomarker testing upfront. And for women with ovarian cancers, we need to know germline bracket status, somatic bracket status and HRD status right at diagnosis. Thank. Speaker 1 You so much for summarizing all that Sharon. With regards to Bevis's map, yes, I want to stress the importance of stopping that about four to six weeks before the surgery to avoid surgical related complications. With regards to the PARP inhibitor story, there are clinical implications. So germline testing, somatic testing is extremely important, but with germline testing there is implications for the family members as well. So this testing cannot be undermined. Sure. And before we move on to the refractory disease that. Speaker 3 Promise we'll move on to the refractory disease, but the reason why you brought up overall survival benefit with a lab rabbit, but you know, we all have our favorite BARP inhibitor or one drug that you rely on just because you're comfortable with or there's data. Sure. And before we move on to that refractory disease, a lab rib root, cap rib or Nerap rib, any clinical pearls around these agents and your preferred agent? Speaker 2 My clinical preference is actually a lab rib. Based on the safety profile, I have the most experience with this particular drug. I also find the side effect profile to be quite well tolerated, so that is my preference. Navigating Platinum-Sensitive and Resistant Ovarian Cancer Now this is a good segue. Let's touch on refractory disease where again we started off by NGS playing a big role. Here we have a few options, TDXDB, RAF MEC inhibitor if you're running into B RAF mutation, but also mirvetuximab should also be on our radar with folate receptor positive disease. Sharon, your treatment paradigm for platinum sensitive and refractory disease. Speaker 2 So it's actually a really exciting time to take care of women with ovarian cancer. I must say based on the maintenance strategies we have upfront with PARP inhibitors and the Paola data, we're seeing so many women that are cancer free so much longer than ever before. It's really exciting. I've seen women with stage 4 ovarian cancer that are N ED-45 years later. The definition of platinum sensitive recurrence is a recurrence greater than 6 six months after finishing the last platinum based therapy. So right now the standard of care is to go back to a platinum doublet plus or minus bevacizumab. My choice is usually carboplatin with DOXIL, usually with bevacizumab. I like that for the safety profile, the schedule, low toxicity. So that's really my preference. Hopefully a patient is not platinum resistant, that means to recur within six months of the last platinum based regimen. But as we all know with ovarian cancer, the troubling part of this disease is eventually all these women become platinum resistant and then we have this nice list of platinum resistant options. I always try to think of clinical trials in the platinum resistant space. There's so many wonderful trials ongoing now with different antibody drug conjugants through Gog partners and such. If a patient has high alpha folate receptor expression in her tumor, she may be a candidate for mirtuximab. That's a great option for women in the platinum resistant space who have had one to three lines of therapy. There's there's so many different options for women. It just depends on platinum sensitive or platinum resistant disease. Speaker 1 And for MSI high disease, we have the option of pembrolizumab and osterolimab, any preferred choice here so? Speaker 2 This immunotherapy really comes into play when we're talking about endometrial cancer that's different than with ovarian cancer. So far the data with immunotherapy and ovarian cancer has been quite disappointing. Right now with advanced or recurrent endometrial cancer, particularly the DMMR patients, it has been standard of care to use dastarlimab or pembrolizumab in combination with platinum based chemotherapy. The role of immunotherapy in advanced ovarian cancer has come into play in the platinum resistant setting when we're using it in combination with, there's one particular paper, for example, looking at immunotherapy KEYTRUDA with bevacizumab and cytoxan. That regimen has had a favorable response rate in the platinum resistant setting. But other than that particular data, by and large, immunotherapy hasn't been quite as promising as we had hoped in this disease. Speaker 3 You know and that's been a little different like you pointed out for endometrial cancer or any other disease site where we see MSI high more often be a colon cancer or for some of our selected patients. Practical Considerations for Treatment and Key Takeaways Before we close, I do want to touch on some common side effects and how to potentially manage these for interventions that we're offering here are not benign with platinum based chemo and Taxol, we have to keep neuropathy and hear a loss in mind. Cryotherapy or compression therapy can help here. With bevacizumabroid, you touched on this already. We have to keep hypertension, bowel perforation and wound healing in mind. So if surgery is in the cards, stopping that bevacizumab at least four to six weeks prior is going to be important. With our PARP inhibitors, a common thing that we have to monitor ends up being cytopenia. Sharon, any final thoughts for our treating physicians here? Speaker 2 So we found that acupuncture is very helpful to prevent neuropathy. We actually have an acupuncturist in our office who gives acupuncture to our patients during the administration of taxol. We've extrapolated that from the breast cancer literature. If any neuropathy still develops, you can always switch to docetaxel. The Scott Rock trial has shown obviously equal efficacy between taxol and docetaxel. So we do use that strategy if needed. And also the importance of biomarker testing upfront. And for women with ovarian cancer, we need to know germline bracket status, somatic bracket status, and HRD status right at diagnosis. So not all HRD tests are the same, like all next Gen. sequencing tests are the same because it's the same technology. But really not all HRD tests are the same. Since ovarian cancer is kind of a rare tumor, really the best HRD test on the market is Myriad's My Choice. It is the companion diagnostic that was utilized in both Prima and Paula and it is an FDA approved pain companion diagnostic. We've had literature looking at head to head comparisons with other companies and we're definitely missing patients when we're using other companies kind of substandard HRD tests. So when we're using a test to talk about making a decision about PARP inhibitors or not, since we now know only HRD positive patients can have Parps, I think it's really important to use the test that really detects HRD the best there's. Speaker 3 So much crossover. We tend to use these medications. Breast cancer or lung cancer? Speaker 2 So. Speaker 3 We have to get comfortable in management. Speaker 2 It's really true. Speaker 3 Sharon, Sharon, thank you so much for sharing your insights and walking us through the current ovarian cancer treatment landscape. For those listening, let us go over our key takeaways from this discussion. Speaker 1 Today we focused on the current treatment landscape of ovarian cancer and for this we had doctor Sharon Lewin, A gynecologist, oncologist to touch on key treatment options from the role of surgery to systemic treatment options and our maintenance options including bevisismap and PARP inhibitors. Speaker 3 Rohat, we also touched on the importance of NGS, but let's not forget that every ovarian cancer patient should be offered germline testing. We also currently have three PARP inhibitors available not only for Bracha mutated disease but also for homologous repair deficient disease, where right now we're stuck with cross trial comparisons and to me the data for a lab prep given overall survival looks the strongest. Speaker 1 To close, we also touched on the refractory disease and some side effects to look out for from our interventions. Thanks so much for joining us to continue our Guinong series. We will be back with endometrial cancer soon. We are the oncology brothers.